Ocular production of interferon-gamma and lack of major histocompatibility complex molecules induce immunological changes in the intraocular environment.
The intraocular immune privilege includes the absence of delayed-type hypersensitivity (DTH) to intraocularly presented antigens. To study the role of major histocompatibility complex (MHC) molecules in relation to the activity of the proinflammatory cytokine interferon-gamma (IFN-gamma) in the maintenance of the intraocular immune privilege, we tested DTH to intraocularly presented antigens in MHC class I- or class II-deficient mice and in transgenic mice with production of IFN-gamma in the retina (rho-gamma). MHC class I- and class II-deficient mice and rho gamma mice with or without additional MHC deficiency developed hypersensitivity to intraocularly presented antigens and increased ocular pathology, whereas control animals did not. The abrogation of the intraocular immune privilege by IFN-gamma was independent of MHC expression and was probably due to disturbance of the blood-retina barrier. The sole lack of MHC class I or II expression produced similar effects, confirming the importance of IFN-gamma and MHC molecules for the development of uveitis.
Geiger
K D
KD
Neurologisches Institut, JWG-Universität, Frankfurt/M., Germany.
Sarvetnick
N E
NE
D000818:Animals; D000956:Antigens, Viral / Q000276:immunology; D018259:Herpesvirus 1, Human / Q000276:immunology; D015395:Histocompatibility Antigens Class I / Q000276:immunology; D000949:Histocompatibility Antigens Class II / Q000276:immunology; D006968:Hypersensitivity, Delayed / Q000276:immunology / Q000473:pathology; D007124:Immunoenzyme Techniques; D007153:Immunologic Deficiency Syndromes / Q000235:genetics* / Q000276:immunology / Q000473:pathology; D007371:Interferon-gamma / Q000096:biosynthesis*; D008285:Major Histocompatibility Complex / Q000235:genetics / Q000276:immunology*; D051379:Mice; D008807:Mice, Inbred BALB C; D008810:Mice, Inbred C57BL; D018345:Mice, Knockout; D012160:Retina / Q000276:immunology* / Q000378:metabolism / Q000473:pathology; D012710:Serum Albumin, Bovine / Q000276:immunology; D014605:Uveitis / Q000276:immunology / Q000473:pathology; D014822:Vitreous Body / Q000276:immunology
D000956:Antigens, Viral; D015395:Histocompatibility Antigens Class I; D000949:Histocompatibility Antigens Class II; D012710:Serum Albumin, Bovine; D007371:Interferon-gamma